Our long-term aim is to provide an in-depth understanding of the relationship between Epstein-Barr virus (EBV) and human disease as a basis of formulating an intervention strategy. Compelling evidence has demonstrated that EBV persists for life following primary infection and is controlled by EBV-specific cytotoxic T lymphocytes (CTLs). Disruption of this delicate balance between virus and host results in an expansion of virus-infected cells which may contribute to a spectrum of clinical disorders including malignancy. The theme of this proposal is to exploit our expertise in the mapping of CTL epitopes and in EBV strain variation to establish a frame of reference to developing a vaccine capable of preventing EBV-associated diseases. Specifically, we propose to: (1)identify the dominant and secondary EBV CTL epitopes using procedures already in use in our laboratories. The techniques involved include T-cell colony formation, Cr release assay, site directed mutagenesis and gene targeting of proteins in transformation and T-cell recognition. (2)determine the extent of EBV strain variation, in particular the variation associated with CTL epitopes. (3)to define the importance of CTL epitopes in the recognition of associated tumors.